Esther F. Freier

Myocardial creatine phosphate and nucleotides in anoxic cardiac arrest and recovery

In isolated perfused dog hearts, myocardial concentrations of creatine phosphate (CrP) and adenosine triphosphate (ATP) decreased following a 45-min period of anoxia. After partial resuscitation by perfusion of oxygenated blood for 30 min, CrP had risen again to approximately control values but ATP concentration had fallen lower. Increased concentrations of deaminated derivatives of ATP, chiefly inosine, were found in the myocardium and in the perfusion effluent after anoxia. The myocardial inosine was still elevated after resuscitation. We conclude that the dynamic equilibrium involving breakdown and resynthesis of ATP through deamination and reamination is disturbed by periods of anoxia as carried out in these experiments and, in addition, inosine is lost by diffusion into extracellular compartments.

Alpha1-Antitrypsin in the Respiratory-Distress Syndrome

Abstract The presence and severity of the idiopathic respiratory-distress syndrome in 34 newborn infants correlated with decreased serum levels of the protease enzyme inhibitor, alpha1-antitrypsin, as compared to 38 normal and sick neonates. These low levels were not the result of a circulating inhibitor or a genetic deficiency of alpha1-antitrypsin production. Serum levels of the inhibitor in survivors returned to normal during the recovery phase of the lung disease. Post-mortem immunofluorescent studies of the lungs of infants who did not survive showed that alpha1-antitrypsin was localized to the hyaline membranes. The intensity of immunofluorescence was comparable to that found for fibrin. The lowered serum level of alpha1-antitrypsin in the respiratory-distress syndrome may be accounted for by the incorporation of this protease inhibitor into the pulmonary hyaline membranes.

The VMA test strip: A new tool for mass screening, diagnosis, and management of catecholamine-secreting tumors☆

Abstract A test strip has been developed for the detection of increased amounts of VMA and metanephrine in the urine. The strip is both inexpensive (less than 15 cents per strip) and simple to use, and is based on the color change of the LaBrosse spot test. It has an acceptable false positive incidence (1:400). It is suggested that such an approach would be useful in decreasing the mortality and morbidity associated with neuroblastoma in childhood, if such a strip were to be employed on a mass screening basis until the child is 7 yr of age. The test strip can also be currently used on a routine basis for follow-up examination in children with previously diagnosed neuroblastoma, and as a screening test for hypertensive patients with a potential for pheochromocytoma, regardless of age.

Extraction and Quantitative Characteristics of Actomyosin in Canine Heart Muscle

The conditions for quantitative extraction of actomyosin from dog heart ventricular muscle were studied. By use of appropriate techniques and conditions, yields of actomyosin comparable to those found by others for a variety of muscles were obtained. The method used could be standardized to give reproducible values with both fresh and frozen muscle. Actomyosin so obtained retained its characteristic properties as evidenced by its viscosity response to ATP and its enzymatic activity.

A system for the analysis of clinical acid-base states based on micromethods for the determination of plasma bicarbonate concentration and blood pH

Abstract A micromethod of analysis of acid-base parameters of capillary blood is presented based on the measurement of blood pH and plasma bicarbonate. From these measurements PCO2 may be derived permitting a complete and unambiguous description of acid-base states with respect to the bicarbonate-carbonic acid system. The method is presented as an alternate one to those described by Astrup 3, 4 and by Singer et al.19 The precision of the method of bicarbonate determination is comparable to that performed on conventional size samples (1 ml or more). A number of factors possibly affecting the accuracy of the method are briefly considered, notably, collection of sample, separation of plasma and cells, temperature of titration, and comparison between capillary and arterial values. Data bearing on these factors and their effects on the validity of the method are presented. Comparative studies with the Astrup3 system of blood pH and plasma pH measurements at different known values of PCO2 and the system involving blood pH and plasma CO2 content by the method of Van Slyke and Neill 2 are presented. The method is proposed as an alternative one to these two systems of deriving acidbase parameters.

Response of Serine Antiproteases to Growth Hormone Therapy in Growth Hormone Deficient Children

Growth hormone regulates the hepatic mRNA levels of alpha 1-antitrypsin and two contrapsin-like mRNAs in the rat. To determine whether growth hormone regulates similar serine protease inhibitors in humans, we measured serum alpha 1-antitrypsin, alpha 1-antichymotrypsin, and antithrombin III by radioimmunodiffusion in 16 growth hormone deficient children before and after growth therapy. Of the 19 determinations made, 17/19 showed an increase in alpha 1-antitrypsin after administration of growth hormone, 198.6 +/- 39.1 mg/dl before growth hormone and 239.4 +/- 44 mg/dl after growth hormone (p = 0.005). Specificity of the response for alpha 1-antitrypsin was indicated by the fact that neither alpha 1-antichymotrypsin or antithrombin III values changed after growth hormone (p = 0.6 and 0.5, respectively). These data are compatible with the hypothesis that growth hormone regulates serine protease inhibitors in humans and suggests that investigation of other members of the serpin gene family might prove fruitful in defining additional growth hormone target genes.

Evaluation of an improved automated carbonateprocedure for serum urate

Summary o 1. An automated method for the determination of serum urate has been adapted from a manual carbonate-phosphotungstic acid method. The method has been evaluated by simultaneously comparing it with a uricase method and the Archibald method. It is sufficiently sensitive, precise and accurate to be used routinely in the clinical laboratory. 2. The importance of avoiding the use of formaldehyde as a preservative in the standard uric acid solution, is emphasized. 3. A significant decrease in non-urate chromogens has been achieved by means of alkali incubation in a time delay coil. 4. An alternative automated uricase procedure is presented for use whenadded specificity is required. 5. The mean serum urate value for 200 male blood bank donors was 5.94(S.D:1.30) mg/100 ml and for 19 female blood donors 4.60 (S.D:1.10) mg/100 ml.

ALPHA-1-ANTITRYPSIN

Publisher Summary This chapter focuses on the experiments related to alpha-1-antitrypsin. Alpha-1-antitrypsin shares some characteristics with enzymes of clinical interest: (1) it is a serum protein that can be quantified in functional terms as an activity in an enzymatic assay; and (2) a great deal of interest, research, and understanding has followed the discovery of an association of this protein with specific disease entities. Cellulose acetate is useful for screening for the homozygous deficient who is at risk for the liver disease if a child or the emphysema if an adult. This should be followed by quantitation either by trypsin inhibitory capacity or with a specific antiserum to alpha-1 antitrypsin either by means of radial immunodiffusion or the rocket electrophoretic technique. One should not assign phenotypes without the typing procedures of the acid starch gel and greater assurance is obtained by rerunning the separated starch gel pattern in an antigen-antibody crossed electrophoretic system with specific antiserum. Alpha-1 antitrypsin is an acute phase reactant protein, so elevated values requiring additional dilution are to be found in inflammatory diseases, cancer, pregnancy, with contraceptive medication, and with stresses such as surgery.